During weeks 53-104 on treatment the rates of adverse events, serious adverse events, serious infections, adverse events resulting in treatment discontinuation, enteric infections, and malignancies were all low and similar to the event rates seen among the patients randomized to placebo in the GEMINI 1 study. The same pattern of low event rates similar to the placebo patients also occurred for episodes of nasopharyngitis, upper respiratory tract infections, Clostridium difficile infections, and tuberculosis cases.
The results also showed better rates of long-term remission and response in the patients who had not previously failed treatment with an anti-TNF drug compared with those who had. Asked what might explain this, Dr. Feagan replied “we know that patients who fail prior drugs are always harder to treat.”
A very similar pattern occurred among the patients with Crohn’s disease who remained on vedolizumab for an additional 52 weeks following completion of a first year of treatment in the GEMINI 2 trial [the Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab in Patients with Moderate to Severe Crohn’s Disease], the pivotal, phase III study that led to the Crohn’s disease indication for vedolizumab (N. Engl. J. Med. 2013;369:711-21). Among 295 GEMINI 2 completer patients who remained on vedolizumab the rate of complete remissions was 57% at entry into the long-term study after 52 weeks on treatment, 64% after 80 weeks on treatment, and 61% after 104 weeks.The overall response rate was 81% at 52 weeks, 78% after 80 weeks, and 74% at 104 week, Dr. Rutgeerts reported. However, he noted that the study design allowed patients who experienced a flare to receive conventional rescue medications and still be counted a responder or in remission, which increased the number of patients in both of these two groups. “Patients did not need to be a responder or in remission at every time point,” he noted.
Once again, the rates of adverse events, serious adverse events, adverse events resulting in drug discontinuation, infections, serious infections, nasopharyngitis, and upper respiratory infection were all similar among patients on long-term vedolizumab compared with control patients with Crohn’s disease, Dr. Rutgeerts said.
The results suggest that with vedolizumab treatment of inflammatory bowel disease “once you achieve an effect it is long-lasting,” Dr. Rutgeerts said in an interview. But he cautioned that the long-lasting efficacy was achieved with treatment every 4 weeks. While this approach was safe, it would also be expensive in routine practice, he noted. “The safety looks good, but the cost would be very high.”
“A key concept of vedolizumab is that it builds efficacy over time,” commented Dr. Silvio Danese during a talk at the meeting. “Vedolizumab is not the fastest runner, but [treating inflammatory bowel disease] is a marathon, and the important thing is getting to the finish,” said Dr. Danese, head of the inflammatory bowel disease unit at the Humanitas Clinic and Research Center in Milan.
Dr. Danese also said that vedolizumab has a safety advantage over anti-TNF drugs when treating ulcerative colitis, although vedolizumab’s efficacy for treating steroid-refractory, fulminant ulcertative colitis remains untested. And he agreed that vedolizumab’s role as a go-to agent for inducing remission in active Crohn’s disease seems questionable.
Two other reports at the meeting further fleshed out vedolizumab’s performance in the GEMINI trials.
One analysis focused on 34 ulcerative colitis patients and 57 Crohn’s disease patients who responded to vedolizumab induction treatment but then lost their response when they subsequently received vedolizumab once every 8 weeks. These patients then switched to a regimen in which they received the drug every 4 weeks, and this resulted in significant reductions in disease activity among some of the ulcerative colitis and Crohn’s disease patients, reported Dr. Séverine Vermeire, a gastroenterologist and professor of medicine at Catholic University in Leuven.
She estimated that roughly a third of patients in both disease categories who lost response when put on the drug once every 8 weeks regained their complete response when their dosing frequency increased to once every 4 weeks.
The findings “suggest that dosing every 4 weeks may be beneficial for certain patients, with no apparent change in safety. These data provide insight into the potential value of dosing every 4 weeks, and in routine practice we will have patients who will lose response when they receive the drug every 8 weeks,” Dr. Vermeire said. “We should try to identify these patients early,” she said, and “we need to investigate why some patients lose their vedolizumab response.” The labeling for vedolizumab calls for treatment once every 8 weeks for maintenance.
